{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T12:27:10Z","timestamp":1768566430207,"version":"3.49.0"},"posted":{"date-parts":[[2023,6,3]]},"group-title":"Neurology","reference-count":50,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>It is increasingly clear that genetic and non-genetic factors account for the association of family history with disease risk in offspring. We sought to distinguish the genetic and non-genetic contributions of family history of stroke and heart disease on incident events by examining adopted and non-adopted individuals.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We examined associations between family history of stroke and heart disease with incident stroke and myocardial infarction (MI) in 495,640 participants of the UK Biobank (mean age 56.5 years, 55% female) stratified by early childhood adoption status into adoptees (n=5,747) and non-adoptees (n=489,893). We estimated hazard ratios (HRs) per affected nuclear family member, and for polygenic risk scores (PRS) for stroke and MI in Cox models adjusted for baseline age and sex.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>12,518 strokes and 23,923 MIs occurred over a 13-year follow-up. In non-adoptees, family history of stroke and heart disease were associated with increased stroke and MI risk, with the strongest association of family history of stroke for incident stroke (HR 1.16 [1.12, 1.19]) and family history of heart disease for incident MI (HR 1.48 [1.45, 1.50]). In adoptees, family history of stroke associated with incident stroke (HR 1.41 [1.06, 1.86]), but family history of heart disease did not associate with incident MI (p&gt;0.5). PRS showed strong disease-specific associations in adoptees and non-adoptees. In non-adoptees, the stroke PRS mediated 6% risk between family history of stroke and incident stroke, and the MI PRS mediated 13% risk between family history of heart disease and MI.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Family history of stroke and heart disease increase risk for their respective conditions. Family history of stroke contains a substantial proportion of potentially modifiable non-genetic risk, indicating a need for further research to elucidate these elements for novel prevention strategies, whereas family history of heart disease represents predominantly genetic risk.<\/jats:p>\n                  <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                    <jats:label>Graphic abstract<\/jats:label>\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"23290649v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.1101\/2023.05.28.23290649","type":"posted-content","created":{"date-parts":[[2023,6,4]],"date-time":"2023-06-04T01:30:21Z","timestamp":1685842221000},"source":"Crossref","is-referenced-by-count":0,"title":["Genetic and non-genetic components of family history of stroke and heart disease: a population-based study among adopted and non-adopted individuals"],"prefix":"10.64898","author":[{"given":"Ernst","family":"Mayerhofer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0605-2381","authenticated-orcid":false,"given":"Livia","family":"Parodi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6116-3020","authenticated-orcid":false,"given":"Kaavya","family":"Narasimhalu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Harloff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marios 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